Massive Life-Threatening Hemorrhages Due to Toxic Oral Intake of 3750 Mg Dabigatran Etexilate As a Suicide Attempt and the Clinical Management

The direct thrombin inhibitor dabigatran etexilate is a novel oral anticoagulant agent. The drug is used for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. There is no specific antidote for the reversal of the anticoagulant effects of dabigatran etexilate. Therefore, the management of the clinical bleeding due to dabigatran etexilate represents a great challenge for the clinician. We would like to share our experience regarding the massive life-threatening hemorrhages due to toxic oral intake of 3750 mg dabigatran etexilate as a suicide attemp and the clinical management.

A 83-year-old man with a medical history of atrial fibrillation, coronary artery disease, hypertension and myelodisplastic syndrome presented to the emergency room with massive hematuria. Because of atrial fibrilation, he was using dabigatran etexilate as a prophylaxis of stroke or systemic embolism. He had received about 50 capsules of dabigatran etexilate (3750 mg) with the purpose of suicide, 30 hours before transfer to hospital. On the admission, physical assessment showed hypotension, massive hematuria and spontaneous pethechial areas and purpuras on the skin. The thrombin clotting time (TT) was 130 s (normal range 20- 30 s), activated partial thromboplastine time (aPTT) was 59 s (normal 22-35 s), prothrombin time - international normalized ratio (INR) was 1,4. Complete blood count showed that hemoglobin was 7,4 g/dL and platelets were 30000 /µL. The patient received 1000 U prothrombin complex concentrates (PCC), for two days. And 2 units of erytrocyte suspensions were administered. The bleeding ceased within the first day and the thrombin time normalized 3 days later.

Dabigatran etexilate is a safer drug than the other anticoagulants. When compared to the warfarin and enoxaparin, dabigatran etexilate has been shown to reduce the rates of bleeding. However, the patients receving dabigatran etexilate have still a risk of bleeding. Because of the predictable pharmacokinetic and pharmacodynamic profile of dabigatran etexilate, there is no need for routine therapeutic coagulation monitoring while using the drug. In case of active bleeding, a possible overdose, or the need for an invasive procedure, the monitoring gains importance. TT and aPTT are the most sensitive laboratory assays to determine the dabigatran etexilate levels. Since the prothrombin time is not affected by dabigatran etexilate, it is not sensitive. There is a strong correlation between the TT measurements and dabigatran etexilate plasma levels. So in monitoring effectivity of therapy or determining the dabigatran etexilate levels in plasma, thrombin clotting time is very useful. However, at dabigatran etexilate concentrations above 600 ng/mL, the maximum measurement of the test is exceeded, correlating to a TT of greater than 120 seconds. Our patient on admission had an elevated TT of >120 seconds indicating accumulation of dabigatran etexilate with levels >600 ng/mL and massive hematuria. There were a bleeding associated dabigatran etexilate and overdose of drug. In order to stop bleeding we need to reverse anticoagulant effects of dabigatran etexilate. There is no specific antidote for dabigatran etexilate and there is limited guidance for treatment in these situations. Fortunately, dabigatran etexilate has short half-life which provides a relatively quick decline in plasma concentrations after discontinuance of the drug in a patient with normal renal function In case of overdose, it is suggested that discontinuing dabigatran etexilate therapy, initiating supportive care, the potential use of hemodialysis, and investigating the source of the bleed. In patients who require more urgent reversal of their anticoagulation, the use of prothrombin complex concentrates (PCCs) may be helpful. PCCs contain vitamin K–dependent coagulation factors II, VII, IX, and X. We started the patient PCCs at the dose of 1000 IU/d and supportive care. The bleeding was ceased in the first day and there was no need to hemodialysis.

Thus, the advantages of using dabigatran etexilate instead of warfarin will lead to widespread use. But it must be kept in mind that dabigatran etexilate is not completely innocent drug and the patients using dabigatran etexilate still have the significant risk of bleeding. And acute reversal of the effects of dabigatran etexilate in the actively bleeding patient is a significant challenge.